Related Experiment Videos
Adhesion molecules involved in macrophage responses to Wallerian degeneration in the murine peripheral nervous system
Abstract:
When a peripheral nerve is damaged the severed axon undergoes Wallerian degeneration. The distal nerve is infiltrated by large numbers of monocyte-derived macrophages which participate in the phagocytosis of degenerating myelin. In other tissues, adhesion molecules play a crucial role in leukocyte recruitment during inflammation. Blood-borne cells enter damaged tissue by interacting with adhesion molecules expressed on activated endothelium. Having crossed the endothelium, leukocytes must adhere and migrate within the tissue. We investigated the adhesion molecules involved in both stages of the macrophage response to transection of one sciatic nerve of BALB/c mice. By injecting monoclonal antibodies in vivo, before and after peripheral nerve injury, we showed that intercellular adhesion molecule-1 (ICAM-1) and integrins alpha4beta1 (VLA-4) and alphaMbeta2 (type 3 complement receptor) are unlikely to be involved in the transendothelial migration of monocytes responding to peripheral nerve degeneration. We also studied the adhesion of macrophages within the endoneurium, using an in vitro adhesion assay. Macrophages showed much greater levels of adhesion to cryostat sections of transected nerves than to control nerves. This increased adhesion was partially inhibited by antibodies to the beta1-integrin chain, and more strongly inhibited by the extracellular matrix molecules fibronectin and collagen. Adhesion was unaffected by laminin-1 and by antibodies to other adhesion molecules, including alpha4beta1- and alpha5beta1-integrins. Thus we conclude that monocyte entry into a degenerating peripheral nerve is independent of alphaLbeta2/alphaMbeta2-ICAM-1 or alpha4beta1/VCAM-1 interactions, and that adhesion within the endoneurium is mediated in part by a beta1-integrin other than alpha4beta1 or alpha5beta1.
Insights
Monocyte infiltration into damaged peripheral nerves does not rely on ICAM-1 or VLA-4. Instead, macrophage adhesion within the nerve involves beta1-integrins and extracellular matrix proteins like fibronectin and collagen.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Peripheral nerve injury triggers Wallerian degeneration, involving macrophage infiltration for myelin phagocytosis.
- Adhesion molecules are critical for leukocyte recruitment and migration into inflamed tissues.
Purpose of the Study:
- To investigate adhesion molecules involved in macrophage recruitment and migration following peripheral nerve transection.
- To elucidate the mechanisms of monocyte transendothelial migration and within-tissue adhesion in nerve degeneration.
Main Methods:
- Used monoclonal antibodies in vivo to block specific adhesion molecules in mice with sciatic nerve transection.
- Performed in vitro adhesion assays using cryostat sections of transected nerves and isolated macrophages.
Main Results:
- Intercellular adhesion molecule-1 (ICAM-1), alpha4beta1 (VLA-4), and alphaMbeta2 integrins were not crucial for monocyte transendothelial migration.
- Macrophage adhesion to damaged nerve tissue was significantly increased compared to control nerves.
- Adhesion within the nerve was partially inhibited by beta1-integrin antibodies and strongly inhibited by fibronectin and collagen.
Conclusions:
- Monocyte entry into degenerating peripheral nerves is independent of ICAM-1, alphaMbeta2, and alpha4beta1/VCAM-1 interactions.
- Adhesion of macrophages within the nerve endoneurium is mediated by beta1-integrins distinct from alpha4beta1 and alpha5beta1, along with extracellular matrix components.